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可变剪接数据库的一项新进展:从目录到对人类可变剪接变体表达和功能调控的详细分析。

A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants.

作者信息

de la Grange Pierre, Dutertre Martin, Correa Margot, Auboeuf Didier

机构信息

INSERM U685/AVENIR, Centre G. Hayem, Hôpital Saint-Louis, Paris, France.

出版信息

BMC Bioinformatics. 2007 Jun 4;8:180. doi: 10.1186/1471-2105-8-180.

Abstract

BACKGROUND

Most human genes produce several transcripts with different exon contents by using alternative promoters, alternative polyadenylation sites and alternative splice sites. Much effort has been devoted to describing known gene transcripts through the development of numerous databases. Nevertheless, owing to the diversity of the transcriptome, there is a need for interactive databases that provide information about the potential function of each splicing variant, as well as its expression pattern.

DESCRIPTION

After setting up a database in which human and mouse splicing variants were compiled, we developed tools (1) to predict the production of protein isoforms from these transcripts, taking account of the presence of open reading frames and mechanisms that could potentially eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated mRNA decay and microRNAs; (2) to support studies of the regulation of transcript expression at multiple levels, including transcription and splicing, particularly in terms of tissue specificity; and (3) to assist in experimental analysis of the expression of splicing variants. Importantly, analyses of all features from transcript metabolism to functional protein domains were integrated in a highly interactive, user-friendly web interface that allows the functional and regulatory features of gene transcripts to be assessed rapidly and accurately.

CONCLUSION

In addition to identifying the transcripts produced by human and mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the putative functions of these transcripts and the regulation of their expression. Therefore, fast DB has achieved an advance in alternative splicing databases by providing resources for the functional interpretation of splicing variants for the human and mouse genomes. Because gene expression studies are increasingly employed in clinical analyses, our web interface has been designed to be as user-friendly as possible and to be readily searchable and intelligible at a glance by the whole biomedical community.

摘要

背景

大多数人类基因通过使用可变启动子、可变聚腺苷酸化位点和可变剪接位点产生具有不同外显子组成的多种转录本。通过众多数据库的开发,人们投入了大量精力来描述已知的基因转录本。然而,由于转录组的多样性,需要交互式数据库来提供有关每个剪接变体的潜在功能及其表达模式的信息。

描述

在建立了一个汇编人类和小鼠剪接变体的数据库之后,我们开发了一些工具:(1)考虑开放阅读框的存在以及可能消除转录本和/或抑制其翻译的机制,即无义介导的mRNA降解和微小RNA,来预测这些转录本产生的蛋白质异构体;(2)支持在多个水平上研究转录本表达的调控,包括转录和剪接,特别是在组织特异性方面;(3)协助对剪接变体的表达进行实验分析。重要的是,从转录本代谢到功能蛋白结构域的所有特征分析都集成在一个高度交互式、用户友好的网络界面中,该界面允许快速准确地评估基因转录本的功能和调控特征。

结论

除了识别由人类和小鼠基因产生的转录本外,快速数据库http://www.fast-db.com还提供了分析这些转录本的推定功能及其表达调控的工具。因此,快速数据库通过为人类和小鼠基因组的剪接变体功能解释提供资源,在可变剪接数据库方面取得了进展。由于基因表达研究越来越多地应用于临床分析,我们的网络界面设计得尽可能用户友好,以便整个生物医学界能够轻松搜索并一目了然地理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a10/1904244/b623b80326b3/1471-2105-8-180-1.jpg

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